JPH0651638B2 - Eye drops for corneal epithelial wound treatment - Google Patents

Description

TECHNICAL FIELD The present invention relates to eye drops effective for healing corneal epithelial disorders,
Particularly, the present invention relates to an eye drop for treating a corneal epithelial wound, which has no side effects in the healing process of the corneal epithelial wound.

(Prior art and problems to be solved) In recent years, new eye drops such as steroids and antibiotics have appeared one after another, but these eye drops are used at high concentration in consideration of permeability into eye tissue. I often do it. Therefore, when treating corneal epithelial wounds by instilling them, some types of eye drops may rather cause delayed wound healing,
Alternatively, there were some that showed side effects such as abnormal regenerated epithelial cells in the defect.

On the other hand, fibronectin, which is a glycoprotein present on plasma and cell surface, is thought to be effective for corneal epithelial wound healing because it promotes the spreading of corneal epithelial cells and enhances the adhesiveness. There is a case applied to.

However, since fibronectin is unstable to heat, it is difficult to sterilize it by autoclaving, and there are also reports that question its effectiveness.

The present inventors have conducted various studies in order to find an effective eye drop for corneal epithelial wounds without the above-mentioned side effects, and as a result, vitronectin, which is a glycoprotein having cell adhesiveness similar to fibronectin, has no side effects. The present invention was found to have an extremely effective healing effect against corneal epithelial disorders, and has completed the present invention. An object of the present invention is to provide an eye drop suitable for corneal epithelial wound healing without side effects. .

(Means for Solving the Problems) The present invention is an eye drop for treating corneal epithelial disorder, which comprises vitronectin.

The corneal epithelial wound to which the eye drop of the present invention is applied refers to a wound generated on the corneal epithelium, erosion, for example, a wound when a traumatic contact lens is mistakenly used, erosion, or so-called dry eye. It refers to wounds and erosions that are found in patients who have difficulty in crying.

Vitronectin is a glycoprotein that exists in the blood of animals and plays an important role in cell adhesion, blood coagulation, immune complement, cancer metastasis, and the like. However, until now, its efficacy as a drug has never been known.

In the present invention, vitronectin is used after being collected and purified from human blood. As a means for collecting and purifying from human blood, as previously proposed by the present inventor, vitronectin present in a living body, for example, plasma is specifically bound to a glycosaminoglycan-immobilized carrier in the presence of urea. The preferred method is to purify (see Japanese Patent Application No. 63-125990). The collected and purified vitronectin is different from the above-mentioned glycoprotein fibronectin, has heat resistance, and can be sterilized by autoclave sterilization to sterilize hepatitis virus and the like, which may be mixed.
It is preferable to use vitronectin that has been subjected to autoclave sterilization. As sterilization conditions, it is preferable to carry out the conditions prescribed by the Pharmacopoeia, for example, 115 ° C. for 30 minutes, 121 ° C. for 20 minutes, and 126 ° C. for 15 minutes.

To obtain the obtained vitronectin as an eye drop, vitronectin with physiological saline or a buffer solution was added at a concentration of 0.1.
μg / m to 500 μg / m, preferably 10 μg / m
Dilute to ~ 200 μg / m. At 0.1 μg / m or less, the effect cannot be expected so much, and at 500 μg / m
Even if the above-mentioned high concentration is used, there is little meaning. And, as the instillation amount, one drop (about 50 μ) at a time is enough several times a day.

Next, an example of the effect of vitronectin on corneal epithelial wound healing will be shown using 12 white rabbits. As an experimental method, a circular corneal epithelial detachment wound with a diameter of 6.5 mm was prepared in the center of the cornea of 12 white rabbits and 24 eyes. Immediately after the production of the detached wound, vitronectin was applied to one eye and physiological saline was applied to the other eye. For vitronectin, vitronectin purified from rabbit plasma was sterilized in an autoclave at 121 ° C. for 20 minutes and diluted with sterile physiological saline to a concentration of vitronectin of 200 μg / m, which was used as an eye drop. The eye drops were applied every 12 hours for 12 hours and thereafter every 6 hours for a total of 48 hours. At the time of instillation, a photograph was taken and the area of the remaining epithelial detachment wound was measured. The results are shown in FIG. In the drawing, the horizontal axis represents the time from the start of instillation, and the vertical axis represents the wound area change rate.

From the above results, 4 to 6 hours after the creation of the epithelial detachment wound, the vitronectin eye drop group had a significantly smaller epithelial defect area than the physiological saline eye drop group, and the vitronectin eye drop wound healing in a rabbit normal corneal epithelium defect model. It was found to be effective early on.

Next, clinical examples using the vitronectin eye drops of the present invention will be shown as examples to explain the present invention more specifically.

Example of clinical use 1. HK female, 35 years old, disease: recurrent corneal epithelial erosion June 9, 1988 The left eye was scratched by a child. He visited a nearby doctor and pointed out the erosion of the corneal epithelium. It improved once, but 1
The epithelium began to peel off once a week. At the same doctor, he received eye drops of vitamins and chondroitin sulfate and eye ointment at night, but repeated recurrence.

Visual acuity 1.0 (n.c.) left 0.6 (n.c.) A punctate superficial membrane inflammation localized to the lower nasal side of the left eye was observed.

Progression: Due to re-exfoliation on September 12, the pathological epithelium was artificially scraped, and the progress of conservative therapy was observed, but the regenerated epithelium was pathological. After 14 days, the pathological epithelium was scraped off again and an attempt was made to instill vitronectin (200 μg / m). 1 after epithelial curettage
Vitronectin was instilled every hour and eye ointment was instilled at bedtime. On 19th, healthy epithelium was regenerated and visual acuity was 1.0 (n.
It improved to c.) and no recurrence is seen until now (10/25).

Judgment: Vitronectin eye drops were effective.

2. SI Male 41 years old Disease: diabetic retinal postoperative corneal epithelial erosion 1975 Diagnosed with diabetes. Insulin used since 1977. 1987 Left eye vitreous hemorrhage. 1988: Repeated vitreous hemorrhage, markedly decreased visual acuity, first medical examination at the University of Tsukuba Hospital.

Sight Right 1.2 (nc) Left 0.06 (nc) September 27, 1988 Performed left eye vitrectomy and ring fastening.
Corneal epithelial erosion appeared after the operation. The erosions gradually expanded, and on October 17, almost all areas of the cornea were eroded.

Process: From October 18, vitronectin eye drops (200 μg / m
) Start. One week after the start of instillation, the epithelium was regenerated throughout the cornea. The regenerated corneal epithelium is currently in a slightly pathological state (October 26), and eye drops continue to be observed.

Judgment: Vitronectin eye drops were effective.

(Effect of the invention) As described above, by using vitronectin as an eye drop, which has not been known to have any effect as a conventional pharmaceutical, an extremely good therapeutic effect on corneal epithelial disorder without showing any side effect. Is played.

[Brief description of drawings]

FIG. 1 is a diagram showing a healing curve when the vitronectin eye drop of the present invention is applied.

Claims (2)

[Claims] 1. An eye drop for treating corneal epithelial wound, which comprises vitronectin. 2. An eye drop for treating corneal epithelial wound according to claim 1, which is vitronekun sterilized by autoclave.